We propose to map the chromosomal location of the genes coding for human immunoglobulin heavy and light chains using somatic cell hybridization techniques. Mouse-human hybrid clones segregating human chromosomes will be examined for the presence or absence of the DNA sequences of the constant region of Kappa, Lambda, and heavy chains of human immunoglobulins. Adult and embryonic nuclear DNA from human lymphoblastoid, normal fibroblasts and transformed lymphocytes, lymphocytes and skin fibroblasts from patients with agammaglobulinemia and their somatic hybrid cells containing selected human chromosomes will be digested with restriction enzymes and the fragments produced resolved on agarose gels. The Southern blots of these DNA fragments will be analyzed for their ability to hybridize with human H and L chain constant region cloned cDNA probes. The concomitant karyological and isozyme analyses of the hybrid cell clones retaining selected human chromosomes for the expression of human constitutive isozyme markers and the presence or absence of human chromosomes should result in the chromosome assignment of the genes coding for immunoglobulins in humans. Finally, we plan to examine the organization and physical map of the H (Mu, Alpha, Gamma) and L (Kappa, Lambda) chain variable and constant region genes in human transformed B cells and normal fibroblasts obtained from patients suffering from agammaglobulinemia, H chain and L chain disorders as well as embryonic derived cells and adult malignant B cells (myeloma, leukemic) and normal (fibroblasts) cells. These results should allow us to determine the spatial organization of any syntenic constant and variable region immunoglobulin structural genes, the relations between gene organization and expression, and whether or not the organization of these genes changes during development or disease states. Additionally, these studies may provide insights as to the molecular basis of agammaglobulinemia and other immunodeficiencies.